Method For Reducing or Eliminating Residue in a Glass Container and a Glass Container made in Accordance Therewith

ABSTRACT

A method of preparing a glass medical container is provided including the steps of providing a glass blank and forming a channel through a part of the glass blank, the channel being substantially free of tungsten or derivatives thereof. In a further aspect of the subject invention, a glass medical container is provided including a glass body having a channel extending through a part of the glass body, the channel being substantially free of tungsten or derivatives thereof. With the subject invention, tungsten or derivatives thereof can be generally or altogether completely avoided in glass medical containers.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.11/664,236, filed Dec. 28, 2007, which is a National Stage Applicationunder 35 U.S.C. § 371 of PCT International Application No.PCT/US2005/035710, filed Sep. 30, 2005, which claims priority to UnitedStates Provisional Application No. 60/614,914, filed Sep. 30, 2004, theentire disclosures of each of which are incorporated by referenceherein.

BACKGROUND OF THE INVENTION

This invention relates to a method for reducing tungsten and derivativesthereof in a glass container and to a glass container with reducedtungsten and derivatives thereof.

Tungsten and derivatives thereof have been commonly used in glassforming techniques. In particular, tungsten-containing pins have beenused in forming shaped apertures or channels in glass structures. Asused herein, the term “tungsten-containing” means tungsten, tungstenplus one or more other materials, or one or more other materials plustungsten, in any combination and percentage. Tungsten has a high fusiontemperature relative to glass and is well suited for glassmanufacturing. Typically, a tungsten-containing pin is used to form anaperture or channel in a glass container, with the glass being thermallyand/or mechanically manipulated about the pin and into conformingengagement therewith. An iterative process can be used where a pluralityof pins are used sequentially to gradually form the aperture or channelin a sequence of manipulations to the glass. With removal of the finalpin, a finished aperture or channel is left in the glass structure. Thistechnique has been commonly used in the formation of glass medicalcontainers, including glass syringe barrels, glass vials, and glass drugcartridge bodies. Each of the glass medical containers (glass syringebarrels, glass vials and glass drug cartridge bodies) includes areservoir for containing a drug, and a channel in communication with thereservoir to provide a means of accessing or removing the drug from thereservoir, typically via a cannula or similar liquid communicationmeans.

It has been found that tungsten-containing pins undesirably leave atungsten-containing residue on the formed glass structures,particularly, portions that had been in contact with the pins, forexample, the aperture or channel. The tungsten-containing residue mayhave detrimental effects on any substance contained or stored within theglass medical container. First, tungsten or derivatives thereof may bedeposited as particulate matter on an inner surface of the aperture orchannel, and such particulate matter may be visible in the containedsubstance. Certain medical procedures require a medical practitioner toview the procedure under magnification, including the administration ofa drug from a glass medical container. The presence of such particulatematter may be dangerous to the patient and may also be disconcerting tothe medical practitioner. Second, drugs containing proteins may beadversely affected by exposure to the tungsten or derivatives thereof.Certain proteins are prone to clump or aggregate about tungsten orderivatives thereof. This clumping or aggregation may lead to a loss inefficacy or other undesirable effects of the drug. In addition, incertain situations, the clumping or aggregation may be so extreme thatsolid fragments may be seen by the naked eye and be disconcerting to apotential user.

Water washing glass medical containers is known in the prior art. Suchwashing techniques have been known to reduce or removetungsten-containing residue. However, washing techniques have inherentlimitations and cannot reliably and repeatedly remove all orsubstantially all tungsten and derivatives thereof from a glass medicalcontainer.

SUMMARY OF THE INVENTION

In one aspect of the subject invention, a method for preparing a glassmedical container is provided including the steps of providing a glassblank and forming a channel through a part of the glass blank, thechannel being substantially free of tungsten or derivatives thereof. Ina further aspect of the subject invention, a glass medical container isprovided including a glass body having a channel extending through apart of the glass body, the channel being substantially free of tungstenor derivatives thereof. With the subject invention, tungsten orderivatives thereof can be generally or altogether completely avoided inglass medical containers.

As used herein, a “drug” is an illustrative and non-limiting term andrefers to any substance to be injected into a patient for any purpose;“tungsten or derivatives thereof” shall mean tungsten or any substancecontaining tungsten, including, but not limited to, tungsten salts andtungsten-containing alloys; and, “substantially free” shall mean a levelof tungsten or derivatives thereof low enough to not detrimentally alteror affect a drug. For example, and by way of illustration and notlimitation, substantially free may mean tungsten or derivatives thereofat a level that the tungsten or derivatives thereof is not visible, doesnot detrimentally alter the efficacy or otherwise adversely effect thedrug, and/or does not detrimentally promote unacceptable levels ofclumping or aggregation of proteins contained in the drug.

These and other features of the invention will be better understoodthrough a study of the following detailed description and accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a plan view of an exemplary glass medical container inaccordance with the subject invention;

FIG. 2 is a schematic showing formation of a channel in a glass medicalcontainer; and

FIG. 3 is a partial cross-sectional view of an alternative channel shapeformed in a glass medical container.

DETAILED DESCRIPTION OF THE INVENTION

With the subject invention, a method is provided for substantiallyreducing or altogether eliminating tungsten or derivatives thereof froma glass container without the need for additional annealing,sterilization or washing steps after the container has been completelyformed. The method is particularly well-suited for use in forming glassmedical containers. For illustrative purposes, an exemplary glassmedical container 10 is shown and described which is in the form of aglass syringe barrel. As can be appreciated by those skilled in the artand from the disclosure provided herein, the glass medical container 10can be any glass body used for containing or storing a liquid and/or drysubstance, including, but not limited to glass syringe barrels, glassvials, and glass drug cartridge bodies.

With reference to FIG. 1, the glass medical container 10 defines areservoir 12 and has a hub 8 with a channel 14 defined therethrough andin communication with the reservoir 12. The glass medical container 10is preferably a unitary glass body. The channel 14 forms an aperture 16at a distal end of the glass medical container 10. The channel 14, viathe aperture 16, provides access to the reservoir 12 and any drug whichmay be contained therein. With the glass medical container 10 being aglass syringe barrel, the channel 14 is formed through the hub 8. Thereservoir 12, as formed in the glass medical container 10, may partlydefine a volume for containing a drug. A piston, plunger, septum, tipcap, stopper, and so forth, may be used in connection with the glassmedical container 10 to form a closed volume for containing a drugwithin the reservoir 12.

With reference to FIG. 2, a process in accordance with the subjectinvention is depicted for forming the channel 14. In particular, a pin20 is provided to form and extend into and possibly through an opening22 defined in a glass blank 24. The glass blank 24 is a partially formedversion of the glass medical container 10. For example, a glass blank 24may comprise a generally cylindrical part having a substantiallyconstant outer diameter, or it may be a partially or completely formedpart having a portion through which the channel 14 is formed anddefined. Thermal and mechanical manipulations are performed on and tothe glass blank 24 to form the final glass medical container 10 as isknown in the art. The opening 22 is in communication with reservoir 26which ultimately, after full formation, results in the reservoir 12.

To form the channel 14, portions of the glass blank 24 about the opening22 are manipulated, either in one process or in iterations, to force theportions of the glass blank 24 into conforming engagement with the pin20. The manipulations may include mechanical manipulations (e.g.,rolling or other shape forming processes) and/or thermal manipulations(e.g., heating glass to a malleable state). In this manner, the channel14 is generally formed with a cross-sectional shape corresponding to theexterior surface of the pin 20. For example, as shown in FIG. 2, the pin20 is shown with a constant cross-section along its length.Correspondingly, as shown in FIG. 1, the channel 14 also has a constantcross-section along its length. Alternative configurations for thechannel 14 are possible. With reference to FIG. 3, the channel 14 isshown with varying cross-sections along its length. This configurationis preferred for staked needle configuration glass syringe barrels,while the constant cross-sectional configuration of FIG. 1 is preferredfor Luer tip mounted needle configurations. With the configuration ofFIG. 3, a first portion 21 of the channel 14 defines a substantiallyconstant diameter D1, while a second portion 23 of the channel 14,located closer to the reservoir 12, defines a substantially constantdiameter D2. The diameter D1 is larger than the diameter D2 with a step25 being formed therebetween. The step 25 acts as a stop against aninsertion of a needle during assembly. The needle is glued or otherwisesecured within the first portion 21 and in communication with the secondportion 23. The channel 14 can take on various configurations (e.g.,more than two diameter changes, tapering, etc.), and, as is readilyrecognized, the pin 20 is shaped externally to achieve the desiredconfiguration of the channel 14. Alternatively, a variety of the pins 20having different diameters may be used to form a channel 14 as shown inFIG. 3, e.g., sequentially.

For typical applications where the glass medical container 10 is a glasssyringe barrel, the channel 14 may have a configuration as in FIG. 1with a continuous diameter of about 1.0 mm; or, the channel 14 may aconfiguration as in FIG. 3 with a diameter D1 of about 0.6 mm, and adiameter D2 in the range of 0.2 to 0.4 mm. Also, the channel 14, as iscommon with glass syringe barrels, defines a diameter smaller than theinternal diameter defined by the reservoir 12. With a vial configurationor a drug cartridge body configuration, the channel 14 may have adiameter generally equal to the internal diameter of the reservoir 12,or even greater than the internal diameter of the reservoir 12.

For the avoidance of tungsten or derivatives thereof in the channel 14,it is preferred that the pin 20 be formed of a material that will notoxidize during the glass forming process described above. Generally, allmaterials can be oxidized, although special circumstances may berequired for oxidation. With the glass forming process discussed abovein connection with FIG. 2, the pin 20 may be thermally manipulated byexposure during thermal manipulation of the glass blank 24 totemperatures in the range of 600° C. to 900° C., and may be subjected toelevated pressures generated by shape-forming tools during mechanicalmanipulation of the glass blank 24. Under these conditions, tungstenoxidizes. Oxidation of prior art pins led to deposition of tungsten orderivatives thereof on portions of the glass blank 24 that were incontact with the pins, particularly the channel 14. In addition, the pin20 is typically used in large scale, repetitious manufacturing andsubjected to fast thermal cycles of heat application and removal,resulting in fatigue to the surface of the pin 20 and consequently, tothe pin 20. Surface fatigue leads to weakening of the structure of thepin 20 and mechanical failure with fragments (typically microscopic)thereof breaking off during use of the pin 20 in the glass formingprocess and, consequently, to deposition of tungsten or derivativesthereof on and within the channel 14.

As indicated above, it is preferred that the pin 20 be formed of amaterial which does not oxidize when subjected to a glass formingprocess which is may be typically conducted under temperatures in therange of 600° C. to 900° C. and under elevated pressure caused byshape-forming tools. These conditions hereinafter shall be referred toas “glass forming process conditions.” It will be obvious to personsskilled in the art that other conditions and parameters may be presentduring the process of forming a glass blank into a glass medicalcontainer. By way of non-limiting examples, materials that will notoxidize under the glass forming process conditions, and useable for thepin 20 in accordance with the present invention, include, but are notlimited to, the following: metals or alloys containing platinum orplatinum group metals; metals or alloys containing nickel; ceramics;silicides; and combinations thereof. It is preferred that the pin 20 beformed of a platinum/rhodium alloy with 80%-90% platinum and 20%-10%rhodium. With the pin 20 being formed of one of the aforementionedmaterials, or other material(s) that will not oxidize under the glassforming process conditions, deposition of tungsten or derivativesthereof on the glass medical container 10 due to the oxidation processcan be avoided. As a result, the channel 14 can be formed substantiallyfree of tungsten or derivatives thereof. It is also preferred that thepin 20 have a melting temperature above the melting temperature of theassociated glass being formed into the glass medical container 10.

An alloy containing tungsten may be used to form the pin 20 where thetungsten-containing alloy does not oxidize under the glass formingprocess conditions. For example, the pin 20 may be formed of with atungsten carbide which does not oxidize under the glass forming processconditions. To further minimize the amount of tungsten or derivativesthereof deposited in the channel 14 in accordance with this embodiment,it is preferred that the pin 20 be formed of a material containing aminimal amount of tungsten, even no tungsten.

In addition to selection of the material from which the pin 20 is made,the present invention may also control the environment in which the pin20 is forming the channel 14 by introducing a controlling gas in thearea of the pin 20 and channel 14. For example, the introduction of aninert gas such as nitrogen gas, by way of non-limiting example, in andaround the area in which the pin 20 is used to reduce the oxygen contentin that area can reduce oxidation of the pin 20.

As will be appreciated by those skilled in the art, the formation of thechannel 14 may require various sequential forming steps includingmultiple pins 20, such as pins 20 of constant or varying diameters. Forexample, the channel 14 may be iteratively formed smaller over asequence of forming stages with increasingly smaller diameter pins 20being used. In each forming stage, the channel 14 is brought intoconforming engagement with the associated pin 20, until a final formingstage is reached. All of the pins 20 used in the various stages in theformation of the channel 14 may be formed of the preferred materialsdescribed above. Alternatively, it has been found that certain formingstages may cause greater deposition of tungsten or derivatives thereofthan other forming stages. For these critical forming stages, it ispreferred that the pins 20 be formed of materials which do not oxidizeunder the glass forming process conditions and which do not includetungsten. The less critical forming stages may use pins formed of anymaterial, including tungsten. With the glass medical container 10 beinga glass syringe barrel and being subjected to multiple forming stagesusing a multiple of the pins 20, it is preferred that the last formingstep utilize the pin 20 being formed of materials which do not oxidizeunder the glass forming process conditions and which do not includetungsten. The preceding forming stages may be formed of any materialsuitable for pin formation. The less critical forming stages may notexpose the pin 20 to the same amounts of thermal and/or mechanicalmanipulation because the channel 14 is only roughly formed and thus maynot contact the pin 20 to the same extent as may occur during the finalforming stage(s).

With the subject invention, the channel 14 can advantageously be formedsubstantially free of tungsten or derivatives thereof. Using thefollowing procedure for measuring concentration, it is preferred thatthe channel 14 have tungsten or derivatives thereof in an amount of 12parts per billion or less. With the preferred process, not only isoxidation of the pin 20 avoided, but the pin 20 may be formed to notdeposit tungsten or derivates thereof even under mechanical failure.This preferred process may produce glass medical containers which haveundetectable levels of tungsten or derivatives thereof. Theseconcentration levels are obtainable with the subject invention on largescale, industrial processes within highly acceptable tolerance levels.Prior art washing techniques have not been capable of obtaining such lowlevels on a repeated, wide-spread consistent basis.

Significantly, the subject invention is able to produce a glass medicalcontainer 10 that is substantially free tungsten or derivatives thereofwithout the need for additional annealing, sterilization or washingsteps. With reference to FIG. 2, the glass blank 24 is an intermediateproduct that is both unsterilized and unwashed. Upon full formation, theglass medical container 10 may be subjected to annealing, sterilizingand air or liquid washing, although such further processing is notalways carried out (such unsterilized containers being referred to as“bulk” processed containers). The sterilizing and washing steps mayprovide for additional removal of any residual tungsten or derivativesthereof which may be present. This residual tungsten or derivativesthereof may have come from the glass raw material, tooling whichcontacts the glass during formation, or tungsten pins used in theprocess. The aforementioned levels of tungsten or derivatives thereof,however, are achieved in accordance with the present invention withoutthe additional annealing, sterilizing or washing processes.

Levels of tungsten or derivatives thereof may be measured by anytechnique. Different techniques may provide different results dependingon how aggressively the tungsten or derivatives thereof is removed fromthe glass medical container for testing (i.e., more aggressivetechniques remove higher levels of tungsten residue). With reference toWang, et al., Journal of Pharmaceutical and Biomedical Analysis, 19(1999) 937-943, “Determination of Tungsten in Bulk Drug Substance andIntermediates by ICP-AES and ICP-MS”, a method of measuring levels oftungsten in drugs is described. Similar methodology can be used formeasuring tungsten-containing residue levels. The inventors hereinrelied on the following procedure to measure the aforementioned levelsof tungsten or derivatives thereof:

1. filling a glass medical container with purified water (e.g., preparedby laboratory purification system, Millipore Milli Ro 4) and sealing theglass medical container (e.g., with a tip cap);

2. placing the filled glass medical container into an ultrasonic bathcontaining water at ambient temperature for 60 minutes;

3. removing the glass medical container and dispensing the containedsolution into a sample vessel; and,

4. measuring the concentration of the tungsten in the solution byInductively Coupled Plasma Mass Spectrometry (ICP/MS).

The aforementioned levels of tungsten or derivatives thereof areactually measured concentration levels of tungsten in the extractedsolution.

What is claimed is:
 1. A method of producing a glass medical container,comprising the steps of: providing a glass bank; providing a pin at anopening in said glass bank; and forming said glass bank to conforminglyengage said pin to form a channel, wherein said pin is made of amaterial that does not contain tungsten and which is selected from thegroup consisting of metals or alloys containing platinum or platinumgroup metals, metals or alloys containing nickel, silicides, andcombinations thereof.
 2. The method of claim 1, wherein said formingstep comprises forming said glass bank to form a channel having a lengthand defining a diameter that is constant along said length.
 3. Themethod of claim 1, wherein said forming step comprises forming saidglass blank to form a channel having a length and defining a diameterthat varies along said length.
 4. The method of claim 3, wherein saidforming step comprises forming said glass blank to form a channel havinga first portion defining a first constant diameter and a second portiondefining a second constant diameter, said first diameter being largerthan said second diameter.
 5. The method of claim 4, wherein said firstconstant diameter is 0.6 mm and said second constant diameter is in therange of 0.2 to 0.4 mm.
 6. The method of claim 1, wherein said glassmedical container is selected from the group consisting of a syringebarrel, vial, and drug cartridge body.
 7. The method of claim 1, whereinsaid forming step comprises thermally manipulating said glass blank. 8.The method of claim 1, wherein said forming step comprises mechanicallymanipulating said glass blank.
 9. The method of claim 1, wherein saidglass blank is unwashed before or after said forming step.
 10. Themethod of claim 1, wherein said glass blank is unsterilized before orafter said forming step.
 11. The method of claim 1, wherein said pin isof a platinum/rhodium alloy with 80% to 90% platinum and 20% to 10%rhodium.